Type 2 diabetes mellitus is a common metabolic disorder affecting over 10 million people in the United States. Twin studies suggest a large familial/inherited component to type 2 diabetes. Additionally, the disorder is heterogeneous and most likely results from the combined effects of a number of predisposing genes (candidate genes), aging and the environment. Type 2 diabetes is characterized by dysfunction of the insulin-producing cells (beta cells), and the body not using the insulin that is present efficiently (insulin resistance). Therefore, candidate genes for type 2 diabetes include those involved with insulin secretion. The sulfonylurea receptor (SuR) falls into this category of candidate genes. The SuR is involved in the release of insulin from the beta cell when blood sugar levels rise or when stimulated by certain diabetes medications. Two changes in the genetic code (DNA) have been identified and are more common in people with type 2 diabetes. We hypothesized that changes in the genetic code of the sulfonylurea receptor produce a defective SuR protein which then contributes to the development of type 2 diabetes through the inability to secrete adequate amounts of insulin to compensate for the body's inefficient use of insulin. To test this hypothesis, we are characterizing insulin secretion and body composition in nondiabetic subjects who have normal SuR gene sequence, and those that have the change in the SuR gene sequence. To characterize beta cell function/insulin secretion, we are performing two tests that measure different aspects of insulin secretion called 1) intravenous glucose tolerance test (IVGTT), and 2) insulin oscillation. To date, 12 subjects have completed the study. Since we have not yet studied enough subjects, comparisions of insulin secretion have not been performed. Through these studies, we will gain a better understanding of the mechanisms by which changes in the SuR gene increase the likelihood of developing type 2 diabetes.